Solving the Mysteries of Heart Disease

by Gerald D Buckberg

  It dawned on us that we rarely operated on the normal, healthy hearts that we studied.

  Instead, we operate on sick and damaged hearts.

  To explore this reality, we would mimic another operation, this time inducing fibrillation with the single momentary electrical stimulus — but in a hypertrophied heart — whose thickened muscle walls mirror those of patients with hypertension, aortic stenosis, heart muscle injury, or heart failure — common illnesses that may need surgical corrective procedures.

  Our first task was to create a heart containing a sick, thickened ventricle. Toward this end, it was our good fortune to have Christof Hottenrott, a research fellow from Germany, working in our lab. During his two years with us, he created hypertrophy in animal test subjects by narrowing their aorta.

  After waiting six to eight weeks for hypertrophy to develop, we then studied ventricular fibrillation after a single momentary stimulus. The ventricle fibrillated on its own for 60 minutes, and heart performance was measured 30 minutes later. This exactly matched how we conducted our studies in normal healthy hearts.

  These results were both disturbing and revealing.

  Our findings mirrored those we found when using continuous fibrillation (continuous current) on the normal heart — as blood flow rate to the inner muscle was the same as to the outer muscle (1:1). But the general medical belief that such “equal flow distribution is fine” is simply incorrect during ventricular fibrillation. We knew a 40% higher flow is needed to the inner muscle to match its greater oxygen demands. That meant an equal flow could not furnish enough oxygen to meet the hypertrophied inner muscles’ need for oxygen (perhaps because thickened muscles were compressing its feeding blood vessels).

  A wide range of damage became evident, as these thick-walled hearts experienced acidosis (excessive acidity), leakage of enzymes, bleeding into its inner wall (hemorrhage), and markedly impaired performance. Studies at postmortem examination showed that these test animals developed the same damage that occurred in patients that succumbed to this injury. (Its elaborate name, hemorrhagic sub-endocardial necrosis, means dead inner wall tissue with bleeding into its cells.) (Figure 2)

  Figure 2: Experimental examples of how the heart appears as you look at it in cross section. The normal heart is shown on the left, and on the right is a thick walled (hypertrophied) heart that underwent ventricular fibrillation. Note development of hemorrhaging (bleeding) and cell death (marked by darkened area) on the inner circumference of the thickened heart — findings that precisely mirror what happens in humans, as described in the last chapter.

  It was now clear to us that the cause of this too-common injury was the dramatic reduction in blood flow to the inner wall of the thickened heart. Yet the need for blood flow to this inner wall is substantially higher (40% more than the outer wall) in a normal heart. (Figure 3)

  Figure 3: Blood flow to inner shell when the whole heart develops ventricular fibrillation (shown in darker columns) and in a beating empty heart (lighter columns). Flow increases markedly (to meet high demands) in normal heart (on left), but this expected increase falls to occur in hypertrophied quivering heart (on right).

  Cracking the Riddle = Wide-Reaching Change

  Our discoveries about ventricular fibrillation became a turning point. The mystery behind why hearts were being “more hurt than helped” was unraveling. My attitude toward the adverse effect of ventricular fibrillation led me to then state that “fibrillation was the F-word.” That belief has never changed.

  Finding these answers established the vital link between the lab and the patient, and the cardiac surgical community responded promptly to our discovery! Our seminal studies resulted in the abandonment of using ventricular fibrillation to stop the heart from beating during aortic valve replacement operations in thickened hearts. They also introduced a wariness about its use in other cardiac procedures (such as coronary artery surgery, and correcting congenital problems).

  Yet despite these two breakthrough studies, I knew there was something else to be found — and it was even more important. While I was pleased that our findings halted a major cause of heart damage, one that I first witnessed starting at Johns Hopkins, a central question remained:

  What should take its place?

  Searching for the Alternative

  With VF no longer an option, we needed to find another way to quiet the heart. Having a “motionless operative field” is important for our technical repairs during cardiac surgery. The only other alternative was to stop the heart from beating by shutting off its blood supply. This is done by placing a clamp on the aorta (while the heart-lung machine takes over to pump oxygenated blood through the rest of the body). An effective method, as the heart muscle stops contracting almost immediately (and rather miraculously, spontaneously begins beating again when the blood supply is returned).

  But a critical issue remained.

  Despite this technique’s ability to achieve a perfectly quiet operative field, hearts become damaged after about 15 minutes of no blood supply.

  Aware of this, many surgeons worked around this 15-minutes ballpark figure by doing a part of the procedure on a stilled heart, then re-nourishing it by restoring blood supply for ten minutes, then shutting it off again to continue their surgery.

  The problem was that while this repeated pattern sounded good in theory, the hearts of our patients were still being damaged.

  From our research, I felt this all pointed toward one thing. Somehow, these hearts were still not being sufficiently nourished during those ten-minute intervals of blood flow. The concept of supply and demand for oxygen re-emerged, just as it did when we developed the DPTI/SPTI ratio (while working with Julien Hoffman at CVRI).

  To make operations safer, we now had two goals: first, to minimize the oxygen needs of the ventricle when the heart is stopped, and second, to optimize nourishment to the inner shell when blood flow is restored.

  An imposing task… but there would be no giving up.

  Minimizing Demand

  We had learned about the oxygen demands of the ventricle in earlier studies, in which “decompressing the ventricle” (done by inserting a tube to drain out or “vent” its blood) would cause a three-fold lowering of its oxygen requirements. Basically, the heart is still pumping, but with no blood in it.

  Cardiac surgeons knew about venting the heart, but often would not do it, as this added an extra step to the procedure. This reluctance was also due to a widespread lack of awareness of how venting reduced the heart’s need for oxygen. However, we knew that it worked by lowering the heart’s energy requirements and thus would enhance the heart’s protection. So we added decompression (venting) to our protocol during clinical surgery.

  Maximizing Nourishment

  As said, I suspected the heart was not being adequately nourished during those intermittent ten-minute periods of restoring blood flow. We wanted to identify the reasons why, and then put in steps to make sure the heart got the best nourishment possible.

  I believed we first needed to keep a sufficient blood pressure so that the heart and all its capillaries were being well fed. This had not previously been a consideration, as maintaining an adequate flow of blood to the body by the heart-lung machine was our top priority.

  So we first established minimums for blood pressure.

  The second objective was that the blood supply from the heart must deliver adequate oxygen. The red blood cell is the vehicle for nourishment, yet many operations were done by adding extra water to the fluid in the heart-lung machine. This was done to avoid adding donor blood into the circuit. But this approach caused anemia (lowering the amount of red cells in the blood), which impaired nourishment by oxygenated blood.

  To accomplish our dual goals (sufficient blood pressure and sufficient oxygen), we created a series of interconnected procedures that safeguarded the heart. These strategies were then combined into protocols that were used in a variety of cardiac operations, that included mitral valve procedures
, aortic valve operations, and coronary artery bypass grafting.

  These new surgical tactics were used in about 300 patients at UCLA, resulting in a dramatic improvement in patient survival — and an impressive reduction in the number of patients that required drugs to support their hearts when the heart-lung machine was disconnected after the operation was complete! (Figure 4)2

  There was great enthusiasm in the department, and as our successes increased — cardiologists realized that we had hit the target and increasingly referred their patients for cardiac surgery to UCLA. Our cardiology and cardiac surgery teams were pleased.

  Figure 4: Our new methods of heart protection in 1972 dramatically reduced the need to support the heart with drugs, compared with findings before 1972. (from 1975 AATS presentation)

  Big Presentation… Big Surprise

  The worldwide problem of cardiac protection was enormous. Its ongoing issues caused the leaders in cardiac surgery to set up a special session at the meeting of the American Association of Thoracic Surgery (AATS) to allow selected members to present different methods of avoiding damage during cardiac repair. This was the first time in the long history of this meeting that people would be pooled from all over the world to address a single topic: myocardial protection. They wanted to get the best people to report what they were doing.

  The leaders of the organization knew we had been conducting numerous studies regarding this at UCLA, and so asked Jim Maloney to chair the conference as he was the head of our division.

  I was thrilled and looked forward to presenting the paper on applying our newly developed methods that essentially eliminated the need to use supportive drugs after a range of cardiac procedures. I felt that our studies had conquered the world’s greatest problem during heart surgery, and wanted to share our findings!

  The meeting took place in New York City in 1975. At this time, my normal dress outfit was a suede coat and open-collar shirt. I also had long hair and a big, broad mustache. I looked like a cross between a hippie and Pancho Villa. (Figure 5a)

  Figure 5a: Dr. Buckberg in his typical dress with suede coat in 1975, before AATS meeting.

  Figure 5b: Dr. Buckberg’s “new” outfit at 1975 AATS. The renegade now dresses “as expected” to let the data do the talking.

  Concerned this might prevent others from taking my message seriously, I got a haircut and trimmed the mustache, and attended the meeting in the same three-piece suit I’d worn to my wedding. (Figure 5b)

  Seeing my new look, several friends asked if I was attending someone else’s wedding.

  “No,” was my answer. “I’m going to a funeral.”

  From my point of view, I was attending a funeral — to bury these ineffective methods of heart surgery and their accompanying damage. All of that would soon come to an end as our new approaches were adopted.

  In preparing his remarks as moderator for the meeting, Jim Maloney asked my advice on what he should say as way of introduction to set the tone for the presentations, since this was my field of interest.

  I pondered this and had a mischievous idea. I created a fictitious but plausible story of Jim Maloney seeking advice from Ernest Starling, a London professor during the early 20th century who was a legend in circulatory physiology. Jim Maloney was supposedly asking for advice on how to remedy the all-too-frequent situation in which patients did poorly after otherwise typical heart surgery procedures.

  Jim Maloney was delighted by the idea, and opened the day’s session by telling my fabricated tale of him speaking with Ernest Starling:

  “Dr. Starling, I’m so glad to consult with you. Today, we see patients whose hearts are not performing normally and we can do all kinds of wonderful operations to correct them. They perhaps have arteries that aren’t getting blood supply — which we fix. They have valves that are leaking or have become narrowed — which we change. There are blue babies with holes in their hearts — and we make them pink again. We do all of these things and the hearts are now technically better — but they look awful. Somehow they’re getting damaged during these procedures and patients have been dying.”

  Dr. Starling was intrigued. “That indeed sounds unusual. How is it you can do all those procedures?”

  “We use something called the heart-lung machine. It takes the blood out of the body and oxygenates it and pumps it back in. So we can exclude the heart from the circulation while we perform surgery on it.”

  “Fascinating. What pressure do you use?”

  “Oh, we don’t look at pressure. We just use the heart-lung machine to maintain a high blood flow.”

  “Really, so what pressure is maintained?”

  “Probably around 30 or 40.”

  “Just 30 or 40? That is called shock, is it not?

  Dr. Starling further asked, “What are the hematocrit numbers?”

  “You mean how many red cells are in the circulating blood? Oh, we don’t worry about that, Dr. Starling. We’re concerned mostly about flow and volume, so we just mix in water to add to the blood.”

  “But that creates anemia, does it not?”

  “I suppose if you want to get technical about it.”

  “Right. And what else happens in these procedures?”

  “Sometimes if we need to quiet the heart while we operate on it, we give the heart a little electric shock to make it fibrillate or slightly quiver so it essentially doesn’t move.”

  “You mean… electrocution as happens with criminals? Dare I inquire what else you do?”

  “Sometimes we go another direction and shut off the blood supply. Completely.”

  “That sounds awful.”

  “Oh, it’s not a problem — because we also expose the heart and then douse it with ice water in order to lower its needs.”

  Starling clarified, “You mean… by freezing it.”

  Jim Maloney then asks Starling, “So that’s pretty much it. What do you think?”

  Dr. Starling considers all this only a moment before he replies:

  “I don’t quite understand. You’re surprised there is a problem?”

  I created this hypothetical story for Jim Maloney to focus upon the outrageous things surgeons were doing to the heart — things everyone thought were so terrific. It was a humorous way to start off this conference’s historical conversation about protecting the heart. Jim Maloney delivered it flawlessly and the audience thought it was hilarious.

  This was followed by numerous presentations of studies addressing the universal problem of heart damage during surgeries. Finally came time for the last paper — mine — on our method of cardiac protection that was producing such great results at UCLA.2 I walked up to the podium and began extolling our noteworthy findings in cardiac surgery to the most well-attended meeting of thoracic surgeons in the world. Over 4,000 people focused on every word I said during my presentation.

  Once finished, I was met with an ovation from the room. This was truly the proudest day of my career to date. I had just made, in my mind, a gargantuan contribution to the future of cardiac surgery.

  I relished this experience as I returned to my seat.

  That feeling lasted all of 15 minutes.

  After my presentation, Georg Rodewald, a surgeon from Hamburg, Germany, approached the stage as he would be the primary discusser of my presentation. He was shaking his head as he passed me in my seat.

  “Why is he doing that?” I wondered.

  Rodewald went on stage to the same podium and began by saying he didn’t understand the need for all the multiple-step solutions I was offering. He simply applied a cardioplegic solution to the heart while shutting off the blood supply to quiet it and saw excellent recovery — despite periods of aortic clamping far beyond 60 minutes.

  I was stunned. Though he hadn’t yet made his research widely public, Rodewald was in effect producing similar results to ours in a much simpler manner while providing a much longer window for a surgeon to perform their procedures.

  I sincerely doubt Dr. Rodewald noticed
my jaw drop. But after all the time and hard work put in to reach our grand solution, his comments were massively deflating.

  Soon after, the conference was over. I could have reacted to this experience in one of two ways. I could have dismissed what he was saying — as do many people in the medical field who reject what’s new and continue doing what they’ve always been doing. But that’s not me. I’m not after what is familiar and comfortable even if it makes me feel good about myself.

  I’m after what works.

  I regarded his new piece of information as a glimpse toward the next peak ahead. On my flight home, Dr. Rodewald’s comments reverberated through me. I knew right then where my research would take me next. I was going to study cardioplegia. I wanted to explore these other ways of stopping the heart. Dr. Rodewald had described a chemical method that he was using in Germany. I also learned that others were exploring this approach in different ways. I wanted to discover what would work best.

  In our research, I had looked at ways to intermittently still the heart between periods of nourishing it with blood. I never looked at ways to simply and safely stop the heart in a prolonged way during a cardiac operation. Now I would investigate how to do this.

  It was a whole new direction.

  I had ascended my first peak, and brought my fellow surgeons up with me, to the benefit of many patients. But now was the time to scale the next mountaintop. Rather than feel threatened by Dr. Rodewald’s findings, I enthusiastically embraced them.

  I couldn’t wait to get home and back into the lab — my bench where new research needed to be done — where we might develop findings that may be converted into a bedside approach that can help patients undergoing cardiac operations.